Probiotic-derived silver nanoparticles target mTOR/MMP-9/BCL-2 - dependent AMPK activation for hepatic cancer treatment

Sep 21, 2026

Recent advances in nanotechnology support new cancer-fighting strategies. Using Lactobacillus acidophilus reducing capacity, silver nanoparticles (AgNPs) are synthesized and investigated for mechanisms involving AMPK/mTOR signaling and BCL-2 expression. The study combines in vitro and in silico work in HepG2 cells, assessing proliferation, autophagy, and apoptosis. The strain is identified via 16S rRNA analysis, AgNP formation is confirmed by FTIR and UV–visible spectroscopy, and apoptosis is evidenced by cell shrinkage and membrane blebbing.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

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Abstract

Introduction

Medical Oncology (2024) 41:106 [https://doi.org/10.1007/s12032-024-02330-8](https://doi.org/10.1007/s12032-024-02330-8) Probiotic‑derived silver nanoparticles target mTOR/MMP‑9/BCL‑2/ dependent AMPK activation for hepatic cancer treatment Alaa Elmetwalli1,2 · Mohamed O. Abdel‑Monem3 · Ali H. El‑Far4 · Gehad S. Ghaith3 · Noaf Abdullah N. Albalawi5 · Jihan Hassan6 · Nadia F. Ismail7 · Tarek El‑Sewedy6 · Mashael Mashal Alnamshan8 · Nouf K. ALaqeel8 · Ibtesam S. Al‑Dhuayan8 · Mervat G. Hassan3 Received: 7 January 2024 / Accepted: 8 February 2024 / Published online: 4 April 2024 © The Author(s) 2024 Abstract Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV–visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC50) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK. Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions. Keywords AgNPs · Apoptosis · Hepatic cancer · Lactobacillus acidophilus · α-SMA · HepG2 * 1 2 3 4 Alaa Elmetwalli [dr.prof2011@gmail.com](dr.prof2011@gmail.com) Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt Microbiology Division, Higher Technological Institute of Applied Health Sciences, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt Botany and Microbiology Department, Faculty of Science, Benha University, Benha, Egypt Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt 5 Department of Nursing, Al Hadithah General Hospital, Al Qurayyat, Saudi Arabia 6 Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt 7 Health Information Management Program, Biochemistry, Faculty of Health Science Technology, Borg El Arab Technological University, Al

FAQs

How are the silver nanoparticles synthesized in this study?

Silver nanoparticles are synthesized using the reducing capabilities of Lactobacillus acidophilus.

What cells and approaches were used to evaluate anticancer effects?

The research uses in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs inhibit proliferation, autophagy, and promote apoptosis in HepG2 cells.

What molecular targets/pathways are proposed for the AgNP anticancer mechanism?

The study links AgNP effects to suppression of AMPK/mTOR signaling and reduced expression of BCL-2, along with related targets such as mTOR and MMP-9, supported by docking results.

Sep 21, 2026

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